Tannic acid attenuates TGF-β1-induced epithelial-to-mesenchymal transition by effectively intervening TGF-β signaling in lung epithelial cells
Tannic acid attenuates TGF-β1-induced epithelial-to-mesenchymal transition by effectively intervening TGF-β signaling in lung epithelial cells
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DOI：
10.1002/jcp.26127
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发表时间：
2018-03-01
影响因子：
5.6
通讯作者：
Rajasekaran, Subbiah
中科院分区：
文献类型：
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作者：
Pattarayan, Dhamotharan;Sivanantham, Ayyanar;Rajasekaran, Subbiah
特发性肺纤维化(IPF)是一种慢性、进行性和不可逆转的肺部疾病，其特征是成纤维细胞和肌成纤维细胞在细胞外基质中聚集。转化生长因子-β1(TGF-β1)诱导的上皮向间充质转化(EMT)被认为是IPF肺成纤维细胞/肌成纤维细胞数量显著增加的可能来源之一。单宁酸是一种天然的膳食多酚化合物，具有多种药理作用。然而，TA是否能抑制转化生长因子-β1介导的肺上皮细胞内膜转化仍是个谜。人肺泡上皮细胞(A549)和正常支气管上皮细胞(BEAS-2B)分别用含或不含TA的转化生长因子-β1处理。结果表明，TA的加入显著抑制了转化生长因子-β1诱导的内皮细胞转化，表现为N-钙粘素、1型胶原、纤维连接蛋白和波形蛋白的表达减少。此外，TA通过诱导细胞周期停滞于G0/G1期，抑制了转化生长因子-β1诱导的细胞增殖。TA能有效抑制转化生长因子-β1诱导的Smad(Smad2和Smad3)、Akt以及丝裂原活化蛋白激酶(ERK1/2、JNK1/2和p38)的磷酸化。另一方面，TA降低了转化生长因子-β1诱导的转化生长因子-β受体表达的增加。通过分子对接、傅里叶变换红外光谱、高效液相色谱和Western印迹分析，进一步证实了TA与转化生长因子β1的直接结合。最后，我们认为TA可能直接与转化生长因子β1相互作用，从而抑制转化生长因子-β信号转导及随后的肺上皮细胞内皮细胞转化过程。还需要进一步的动物研究来阐明其在肺纤维化中的潜在治疗益处。
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-to- mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects. However, whether TA can inhibit TGF-beta 1-mediated EMT in lung epithelial cells remains enigmatic. Both the human adenocarcinomic alveolar epithelial (A549) and normal bronchial epithelial (BEAS-2B) cells were treated with TGF-beta 1 with or without TA. Results showed that TA addition, markedly inhibited TGF-beta 1-induced EMT as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin, and vimentin. Furthermore, TA inhibited TGF-beta 1-induced cell proliferation through inducing cell cycle arrest at G0/G1 phase. TGF-beta 1-induced increase in the phosphorylation of Smad (Smad2 and 3), Akt aswell as that ofmitogen activated protein kinase (ERK1/2, JNK1/2, and p38) mediators was effectively inhibited by TA. On the other hand, TA reduced the TGF-beta 1-induced increase in TGF-beta receptors expression. Using molecular docking approach, FTIR, HPLC and Western blot analyses, we further identified the direct binding of TA to TGF-beta 1. Finally, we conclude that TA might directly interact with TGF-beta 1, thereby repressing TGF-beta signaling and subsequent EMT process in lung epithelial cells. Further animal studies are needed to clarify its potential therapeutic benefit in pulmonary fibrosis.